This invention relates to a process for Zr-mediated hydroboration of alkynes which offers (E)-vinylboronic esters in high yield with stereoselectivity and regioselectivity.
The formation of new asymmetric carbon-carbon bonds can be readily accomplished using a wide range of palladium-catalyzed cross coupling reactions. One of these processes involves the cross coupling reaction of an organometallic derivative with an alkyl or aryl halide with organoborane.
As one type of frequently used synthetic building block, vinylboronic esters can be prepared by hydroboration of alkynes using catecholborane, under harsh reaction conditions.
Preparation of pinacolborane was reported in 1992 and can be used in place of catecholborane. Pinacolborane has an advantage over catecholborane by providing mild reaction conditions, high functional group tolerance and excellent stability.
The transition metal complex catalyzed hydroboration of alkynes includes development of new methodologies and mechanistic studies. Schwartz Reagent (Cp2ZrHCl) has been used to catalyze hydroboration of alkynes with pinacolborane at room temperature. It was found that hydroboration of less reactive alkynes by this method can be sluggish and stereoselectivity towards E-vinylboronic esters is unsatisfactory, especially for oxygen-containing alkynes.
The process of this invention provides a Zr-mediated hydroboration which offers (E)-vinylboronic esters in high yield and excellent stereoselectivity and regioselectivity.